If sib is "clear" do I need to test brother?

[jules]

how can one family of basenjis have the majority of them come back indeterminate? this puzzles me as one did come back affected

[EskiLovr]

I have some knowledge of genetics, and I can explain a little about the 'indeterminate' finding. Fanconi is not a single loci disorder. Multiple genes in several locations are involved in a 'probably affected' result. 'Indeterminate' results usually carry affected type results in some of the locations, but not all of them.

Hope this helps

[lvoss]

That is not correct, Fanconi is believed to be a single locus disorder but the locus has not been precisely indentified at this time. The current test is not testing for the actual gene which has not yet been discovered but instead uses three markers that are a located in close proximity to the gene. When 1 or more of these markers separates from the others due to crossing over during Prophase I of meiosis there is no way to tell which markers the gene went with.

[EskiLovr]

Then where does the "indeterminate" result come from?

[lvoss]

The "interdeterminate" result comes when a dog has inherited an incomplete set of markers. When this happens there is no way to know whether they have the inherited the gene with the partial set of markers or not so they are labeled "indeterminate".

[jules]

im still confused, how can you have indeterminate between clear and carrier but not between carrier and affected and why does a lot of family members come back as indeterminate between clear and carrieri could understand if it was only one or two but it is most of them

[EskiLovr]

Since this is just a marker test, "Indeterminate" results mean that some of the markers are found, and some are not. So the gene could be present, or not present. Indeterminate actually could be affected, carrier or clear, it is just not possible to tell, because the markers are incomplete.

Marker testing is a little trickier than direct testing. It is good, but there are holes in the test, since the genes and markers aren't totally "fixed" in their positions on the genome. Markers and the genes they are used to track can become separated by mutations.

[lvoss]

@jules:

im still confused, how can you have indeterminate between clear and carrier but not between carrier and affected and why does a lot of family members come back as indeterminate between clear and carrieri could understand if it was only one or two but it is most of them

I was at the 2007 Nationals and asked about this and they said that they just haven't seen any Indeterminate between Carrier and Affected at that time. I find that hard to believe also but the lab is sticking to that explanation.

As far as some families have lots of IND, an IND has 1 set of markers for Clear and one IND set so when bred according to the guidelines they will produce either Clear or IND offspring. It also seems that in some families that area is more prone to changes so high rates of IND occur. The lab is working to zero in on the gene so all of the IND results can be resolved.

[jules]

well i know of one family that produced affected and IND in the same litter that was why i was asking i will be glad when the gene is found then we can all be sure

[lvoss]

A carrier can produce, Carriers, Affecteds, Clears, and IND depending on who they are bred to.

[jules]

what about a carrier to an IND

[lvoss]

I have seen them produce Affected but those dogs really should be Indeterminate between Carrier and Clear but the lab never responded about that.

The possible outcomes should be Clear, Carrier, IND, Indeterminate between Carrier and Affected based on the explanation the lab has given us.

[jules]

i have seen ind and affected in the same litter